Deceased- and living-donor kidney allograft recovery

INTRODUCTION — Until totally implantable bioartificial or laboratory-grown kidneys become available, transplant surgeons must retrieve kidneys from deceased or living donors. An enormous part of the success of kidney transplantation is predicated on the technically perfect recovery of the kidney [1-3]. The technical aspects of deceased- and living-donor kidney allograft recovery will be discussed here.

DECEASED-DONOR KIDNEYS — Most of the time, a number of different organs will be recovered from a single deceased donor, potentially including the heart, lungs, liver, pancreas, kidneys, and intestine [4,5]. The kidneys can be reliably predicted to be the last organs to be removed.

Technique — The deceased donor will have been given heparin and possibly phentolamine (to promote vasodilatation) prior to aortic cross clamping. Donor pretreatment with dopamine may decrease the requirement for dialysis after kidney transplantation [6]. In a randomized, prospective study, for example, the administration of low-dose dopamine (4 mcg/kg per minute) for a median period of 344 minutes resulted in a decreased need for multiple dialyses posttransplant (25 versus 35 percent, 95% CI 0.35-0.83) [6]. Thus, with respect to donor management, a low threshold should exist to initiate low-dose dopamine early in the donor transplant management.

Via a cannula placed in the distal aorta, the kidneys are kept cold by an in situ flush with an intracellular type of preservation solution. In the United States, the most popular is the University of Wisconsin (UW; Viaspan) solution; however, there has been an increase over the past several years in the utilization of histidine-tryptophan-ketoglutarate (HTK) solution as an alternative. There is some evidence that the HTK and UW solutions provide similar patient and allograft survival rates [7]. The kidneys are usually not seen or mobilized prior to aortic cross clamping, as such manipulation can adversely affect the liver.

Once the thoracic and upper abdominal organs have been removed, the right colon and distal small bowel are mobilized medially and superiorly, and the right kidney is exposed. The right kidney is then mobilized medially, with Gerota's fascia, from the retroperitoneum. The left colon is then mobilized medially and superiorly, and the lower splanchnic nerves are divided. The left kidney, again with Gerota's fascia, is mobilized medially.

Next, the ureters are divided near their insertion into the bladder and are mobilized with generous amounts of periureteral tissue up to the level of the lower pole of the kidneys. The distal aorta is then divided below the cannula, and the inferior vena cava is divided just above the confluence of the common iliac veins. All four structures (ie, the two ureters, vena cava, and aorta) are held up together with clamps, and dissection is carried out superiorly, directly on the spine, to a point above the renal artery and vein orifices. The suprarenal aorta and vena cava are then transected and any additional connective tissue divided. Both kidneys are then removed en bloc and placed in a basin of ice-cold solution.

At this point, the kidneys can be separated (although very small pediatric kidneys [from donors less than one to two years of age] may be kept together and transplanted en bloc). The left renal vein is dissected free at its insertion into the inferior vena cava, and a cuff of vena cava containing the left renal vein orifice is excised, leaving the remainder of the vena cava with the right kidney. The left renal vein can then be dissected free beyond the aorta.

The kidneys are then flipped over, and the posterior aorta is divided between the lumbar arteries. The renal artery orifices can now be identified. The kidneys are then flipped over again, and the anterior aorta is divided in half longitudinally. A small amount of remaining connective tissue will remain, which is easily divided.

The kidneys are now completely separated. Most of Gerota's fascia is then removed from each kidney to ensure proper cooling of the kidney. The anatomic structures are described, and the renal arteries are flushed with 250 mL of chilled UW or HTK solution prior to packaging the kidneys. It is important that excessive fat be removed prior to packaging so that the fat does not act as an insulator, preventing uniform and rapid cooling of the entire kidney.

With pulsatile preservation, the separated or unseparated kidneys are placed in a special cassette, and the aorta or renal arteries are connected to the pulsatile preservation tubing. In this setting, much of the back-table dissection may need to be performed early. (See "Kidney transplantation in adults: Overview of the surgery of deceased donor kidney transplantation".)

In the case of donor kidneys of questionable viability, wedge biopsies of the kidneys can be performed for histologic evaluation prior to packaging or placement on the pulsatile preservation apparatus.

Pulsatile perfusion — Machine or pulsatile perfusion, versus cold storage, may reduce the incidence of delayed graft function and improve allograft survival:

●In one trial, one kidney from 366 consecutive deceased donors was randomly assigned to machine perfusion and the other kidney to cold storage [8]. The outcomes of patients who received these 672 kidneys were subsequently evaluated at one year. Compared with cold storage, machine perfusion significantly reduced the incidence of delayed graft function from 26.5 to 20.8 percent (adjusted odds ratio [OR] 0.57, 95% CI 0.36-0.88) and improved allograft survival at one year (94 versus 90 percent).

The effect of the preservation method on delayed graft function did not differ significantly between patients who received kidneys from donors after brain death and patients who received kidneys from donors after cardiocirculatory death. There was also a nonsignificant trend toward an increased incidence of primary nonfunction in the cold-storage group (4.8 versus 2.1 percent, p = 0.08).

In a follow-up report of this study, the three-year graft survival was better for machine-perfused kidneys compared with cold storage (91 versus 87 percent, adjusted hazard ratio [aHR] for graft failure of 0.60) [9]. Subgroup analysis showed improved three-year survival associated with machine perfusion for expanded-criteria kidneys (86 versus 76 percent, aHR of 0.38) and for kidneys donated after brain death (91 versus 86 percent, aHR 0.54) but not for kidneys donated after circulatory death. There was no difference between groups in patient survival.

●A meta-analysis that included 7 randomized clinical trials (RCTs) and 11 non-RCTs demonstrated a reduced risk of delayed graft function associated with machine perfusion compared with cold storage (relative risk [RR] 0.81, 95% CI 0.71-0.92) [10]. There were no differences between groups in the rates of patient survival, acute rejection, or long-term graft function in this analysis.

●The effect of pulsatile perfusion on delayed graft function was examined in a study of 94,709 deceased-donor transplants stratified on the basis of cold ischemia time [11]. Among recipients of standard-criteria kidneys, pulsatile perfusion was associated with a reduction in delayed graft function across all cold ischemia times. Among recipients of expanded-donor kidneys (ECD) and donation after cardiac death (DCD) kidneys, pulsatile perfusion was associated with decreased delayed graft function when cold ischemia time was >6 hours and between 6 and 24 hours, respectively. Criteria for ECD and DCD kidneys are discussed elsewhere. (See "Management of the deceased organ donor" and "Kidney transplantation in adults: Organ sharing", section on 'Kidney donor profile index (KDPI)'.)

Machine perfusion may also provide better protection against delayed graft function when compared with therapeutic hypothermia (see 'Therapeutic hypothermia' below). In one trial, 1349 kidneys from 725 brain-dead donors were randomly assigned to machine perfusion (511 kidneys), therapeutic hypothermia (359 kidneys), or combination therapy with both (479 kidneys), before transplantation [12]. The incidence of delayed graft function among the kidney transplant recipients was 19 percent in the machine perfusion group compared with 30 percent in the therapeutic hypothermia group and 22 percent in the combination therapy group. Rates of allograft survival at one year were similar among the three groups.

Although the magnitude of benefit is not large, there appears to be enough benefit associated with pulsatile preservation to justify its continued use in routine clinical practice.

Machine perfusion adds significant expense to kidney retrieval. However, the reduction in delayed graft function would significantly mitigate this increased expense by reducing the increased costs of delayed graft function.

Therapeutic hypothermia — The standard protocol for management of deceased-donor kidneys mandates that retrieval of organs be done under normothermic conditions. Therapeutic hypothermia (or targeted temperature management) may decrease the risk of delayed graft function. This was shown in a trial in which 370 organ donors (resulting in 572 kidney transplants) were randomly assigned after declaration of brain death to organ retrieval under normothermic (36.5 to 37.5°C [97.7 to 99.5°F]) or hypothermic (34 to 35°C [93.2 to 95°F]) conditions [13]. The targeted temperature management protocol was initiated immediately after authorization for organ donation and ended when the deceased donor went to the operating room for kidney retrieval.

Delayed graft function occurred less frequently in the hypothermic compared with the normothermic group (28 versus 39 percent, respectively), with an OR of 0.62 (95% CI 0.43-0.92), after adjusting for donor type (expanded criteria or standard criteria), creatinine, and age; kidney cold ischemia time; and organ procurement agency. The benefit of hypothermia was even greater among recipients of expanded-criteria kidneys (31 versus 57 percent among normothermic donors), with adjusted OR of 0.31 (95% CI 0.15-0.68). Among standard-criteria donors, there was a trend toward decreased risk of delayed graft function in the hypothermic group that was not statistically significant (adjusted OR 0.71, 95% CI 0.45-1.13). The study was terminated at the recommendation of an independent safety monitoring board after interim analysis demonstrated a benefit.

The mechanisms by which hypothermia confers a protective effect are not known but may involve better preservation of ATP, reduction of apoptosis and/or free radical generation, or decreased inflammation and/or coagulation.

The long-term effects of hypothermia on graft survival or acute rejection were not tested by this trial. In addition, confidence in the reported result may be slightly limited by confounding by a reduced cold ischemia time among kidneys from hypothermic donors (which could have contributed to decreased delayed graft function). However, these promising data suggest an inexpensive and safe intervention that may increase graft survival [14].

LIVING-DONOR KIDNEYS

Open technique — There are a few technical variations regarding the performance of an open donor nephrectomy [5,15]. In most cases, the living donor is placed on his/her side, and the table is maximally flexed under the 12^th rib to expose the space between the ribs and the iliac crest. The kidney bar may be raised underneath the 12^th rib to improve the exposure. The incision may be rib sparing, below the 12^th or 11^th rib, or may involve the removal of one or more ribs to facilitate exposure of the kidney and the renal hilum.

A flank incision is made, commonly from the lateral order of the left rectus, at the level of the umbilicus, to a point underneath the 12^th rib. The subcutaneous and fascial layers are incised to the level of the peritoneum, and the latter is mobilized medially and anteriorly to expose the ureter. The ureter is dissected free for a short distance, and the kidney is then dissected free from the Gerota's fascia. The kidney will come down as it is dissected free. The ureter is then mobilized superiorly, and the renal vein and artery are dissected free. Periarterial papaverine is infiltrated to prevent arterial spasm, and the branches of the renal vein are divided between ligatures, as needed, to obtain adequate length. The ureter is then dissected free distally to the level of the bifurcation of the common iliac artery. Care is taken not to dissect too closely near the ureter to minimize the risk of devascularizing it. The distal ureter is clamped and divided, ligated distally, and tagged at the proximal end with a small clamp. During the course of the dissection, small doses of intravenous furosemide (5 mg) and mannitol (12.5 to 25 grams) are administered, along with a sufficient volume of intravenous fluid, to ensure a brisk diuresis of the kidneys.

When the recipient is ready and the donor kidney has been completely mobilized, the proximal renal artery is clamped and divided, the distal renal vein is then clamped and divided, and the kidney is removed. The kidney is then flushed on the back table with a cold solution containing heparin (a locally used example is Ringer's lactate with 10,000 units of heparin/liter) and taken to the adjacent operating room to be transplanted. In this manner, systemic heparinization of the donor is avoided (although some surgeons still anticoagulate the donor with heparin). After removal of the kidney, the donor artery and vein stumps are securely oversewn and ligated, hemostasis is achieved, and the wound is closed using standard techniques.

Laparoscopic-assisted technique — Laparoscopic-assisted donor nephrectomy has become the preferred technique in some centers [16-21]. The positioning is similar to that utilized for the open technique, but instead of the open retroperitoneal exposure of the kidney, an intraperitoneal approach is employed. With the laparoscopic-assisted technique, three to five trocars are inserted to establish ports, ranging in size from 5 to 12 millimeters. One port is used for carbon dioxide insufflation, one for a video camera, and the others for the laparoscopic surgical knife and clamps (the carbon dioxide can usually be attached to a trocar being used for another purpose). After insufflation with carbon dioxide to a pressure of approximately 10 to 15 mmHg, the left colon is mobilized medially to expose the kidney, and the splenorenal ligament is divided. Laparoscopic dissection is then used to mobilize the kidney and expose the artery, vein, and ureter. (See "Kidney transplantation in adults: Benefits and complications of minimally invasive live-donor nephrectomy".)

As with nonlaparoscopic techniques, there are similar issues with laparoscopy regarding small doses of intravenous diuretics, mannitol, and periarterial papaverine. Intravenous volume requirements may be greater than those utilized in open cases to counteract the effect of the intraperitoneal gas on renal blood flow. As an example, a donor will commonly receive 4 to 6 liters of isotonic fluids to maintain urine output above 50 cc per hour. When the kidney is ready to be removed, a small (5 to 7 cm) incision is made to allow for basketing and removal of the kidney after stapling the artery and vein. The use of Weck Hem-o-lok surgical clamps to ligate the renal artery has been associated with life-threatening hemorrhage among patients undergoing laparoscopic kidney donation, and they are contraindicated for this use. The US Food and Drug Administration (FDA) has issued an alert that these clamps not be used for ligation of the renal artery during laparoscopic living-donor nephrectomies [22].

Individual centers differ with regard to the location of the incision, the administration of systemic heparin, and the use of a hand-assisted technique to help with mobilization and removal of the kidney. Some centers use a retroperitoneal laparoscopic approach, but this is less common.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Kidney transplantation".)

SUMMARY

●Deceased-donor kidney recovery – A kidney is recovered from a deceased donor after the donor has been given heparin, and often phentolamine, to promote vasodilatation. Donor pretreatment with dopamine may decrease the requirement for dialysis after kidney transplantation.

Prior to removal from a deceased donor, the kidneys are kept cold by an in situ flush with an intracellular preservation solution that is either the University of Wisconsin (UW; Viaspan) solution or histidine-tryptophan-ketoglutarate (HTK) solution. Kidneys are removed en bloc and placed in ice-cold solution prior to being separated. Gerota’s fascia and excessive fat are removed to ensure proper cooling of the kidney, and the renal arteries are flushed with chilled UW or HTK solution prior to packaging. (See 'Deceased-donor kidneys' above and 'Technique' above.)

●Living-donor kidney recovery – Donor nephrectomy from a living donor may be done via an open or laparoscopic-assisted technique. Whereas the open technique utilizes retroperitoneal exposure of the kidney, the laparoscopic technique employs an intraperitoneal approach.

In both open and laparoscopic techniques for kidney dissection from a living donor, intravenous furosemide (5 mg) and mannitol (12.5 to 25 grams) are given with intravenous fluid to ensure a brisk diuresis of the kidneys. Intravenous volume requirements may be greater when a laparoscopic technique is used. Individual centers differ with regard to the location of the incision, the administration of systemic heparin, and the use of a hand-assisted technique to help with mobilization and removal of the kidney. (See 'Open technique' above and 'Laparoscopic-assisted technique' above.)